GRIN2A

Summary

GRIN2A (glutamate ionotropic receptor NMDA type subunit 2A, HGNC:4585) is a protein-coding gene on chromosome 16p13.2, encoding Glutamate receptor ionotropic, NMDA 2A (Q12879). Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2903 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 31
• Clinical variants (ClinVar): 2,441 total — 154 pathogenic, 137 likely-pathogenic
• Phenotypes (HPO): 109
• Druggable target: yes — 37 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001134407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4585
Approved symbol	GRIN2A
Name	glutamate ionotropic receptor NMDA type subunit 2A
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Aliases	GluN2A, NR2A
Ensembl gene	ENSG00000183454
Ensembl biotype	protein_coding
OMIM	138253
Entrez	2903

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000330684, ENST00000396573, ENST00000461292, ENST00000463531, ENST00000535259, ENST00000562109, ENST00000566665, ENST00000566670, ENST00000566683, ENST00000568247, ENST00000636273, ENST00000636406, ENST00000637188, ENST00000637334, ENST00000637393, ENST00000674742, ENST00000675189, ENST00000675398, ENST00000676032

RefSeq mRNA: 3 — MANE Select: NM_001134407 NM_000833, NM_001134407, NM_001134408

CCDS: CCDS10539, CCDS45407

Canonical transcript exons

ENST00000330684 — 13 exons

Exon	Start	End
ENSE00001291739	9753408	9764948
ENSE00001304023	9798277	9798464
ENSE00001306768	9840647	9840800
ENSE00001308193	9849756	9849961
ENSE00001320221	9768851	9769089
ENSE00001323909	9834105	9834230
ENSE00001326287	9829423	9829652
ENSE00001327113	9822264	9822424
ENSE00001330010	9840936	9841104
ENSE00001525491	10181877	10182428
ENSE00001525515	10179998	10180429
ENSE00003507434	9937959	9938551
ENSE00003553629	9890986	9891100

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5518 / max 86.1217, expressed in 224 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156195	0.5534	117
156197	0.2637	105
156193	0.1773	75
156194	0.1762	73
156191	0.1582	56
156190	0.0951	43
156196	0.0543	33
156192	0.0345	28
156186	0.0198	13
207748	0.0193	15

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.87	gold quality
endothelial cell	CL:0000115	97.67	gold quality
middle temporal gyrus	UBERON:0002771	96.92	gold quality
postcentral gyrus	UBERON:0002581	94.75	gold quality
parietal lobe	UBERON:0001872	94.60	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.02	gold quality
superior frontal gyrus	UBERON:0002661	93.78	gold quality
primary visual cortex	UBERON:0002436	93.25	gold quality
occipital lobe	UBERON:0002021	92.91	gold quality
entorhinal cortex	UBERON:0002728	91.82	gold quality
frontal pole	UBERON:0002795	88.44	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.41	gold quality
prefrontal cortex	UBERON:0000451	87.35	gold quality
frontal cortex	UBERON:0001870	86.48	gold quality
cerebellar vermis	UBERON:0004720	85.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.64	gold quality
neocortex	UBERON:0001950	84.54	gold quality
cerebral cortex	UBERON:0000956	84.06	gold quality
lateral globus pallidus	UBERON:0002476	83.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.23	gold quality
right frontal lobe	UBERON:0002810	81.44	gold quality
Ammon’s horn	UBERON:0001954	81.14	gold quality
temporal lobe	UBERON:0001871	80.71	gold quality
telencephalon	UBERON:0001893	79.87	gold quality
germinal epithelium of ovary	UBERON:0001304	79.53	gold quality
cerebellum	UBERON:0002037	79.20	gold quality
cerebellar cortex	UBERON:0002129	78.97	gold quality
cerebellar hemisphere	UBERON:0002245	78.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.22	gold quality
cingulate cortex	UBERON:0003027	78.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1870.59
E-HCAD-35	yes	29.90
E-ANND-3	yes	7.46
E-MTAB-7303	no	124.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, FOSB, MYCN, NRF1, SP4

miRNA regulators (miRDB)

316 targeting GRIN2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4789-3P	99.99	70.75	2484

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The C-terminus of NR2A is critical for modulation of desensitization by calcineurin. (PMID:11985816)
• The levels of NR2A mRNA are decreased in Alzheimer disease hippocampus and entorhinal cortex compared to controls. (PMID:12127670)
• In schizophrenia, analysis of the GRIN2A gene detected four single nucleotide polymorphisms, and a variable (GT)(n) repeat in the promoter region. (PMID:12724619)
• human cerebral endothelial cells express the message and protein for NMDA receptors. (PMID:12893641)
• N-methyl-d-aspartate receptor subunit messenger ribonucleic acids are differentially expressed during postnatal development of the human hippocampus (PMID:12956718)
• Owing to its role in aspects of cognition, linkage of 4 GRIN2A polymorphisms was studied in inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes. (PMID:14699423)
• disulfide bridging and structural integrity within the NR1 N-terminal domain is requisite for cell surface N-methyl-D-aspartate receptor expression (PMID:14732708)
• genetic variation in GRIN2A may confer increased risk for attention deficit disorder with hyperactivity (PMID:14966475)
• NR2A subtypes mainly expressed in the striatum, may influence the variability in age of onset of Huntington disease. (PMID:15742215)
• a probable genetic effect for the GRIN2A promoter (GT)n variation on the predisposition to schizophrenia in Japanese cohorts. (PMID:15774266)
• Analysis of the autistic disorder susceptibility locus suggests an association on chromosome 16p between GRIN2A and ABAT. (PMID:15830322)
• the conformation of NR1 subunit homodimers is affected by the partner NR2 subunits during the formation of heteromeric receptor complexes (PMID:15888440)
• GRIN2A and TCERG1 may show true association with residual age of onset for Huntington’s disease in genetic association tests in 443 affected people from a large set of kindreds from Venezuela. (PMID:17018562)
• analysis of the role of the glutamate binding pocket in agonist affinity and efficacy of N-methyl-D-aspartate receptor activation (PMID:17105731)
• the three amino acid tail following the TM4 region of the N-methyl-D-aspartate receptor (NR) 2 subunits is sufficient to overcome endoplasmic reticulum retention of NR1-1a subunit (PMID:17255096)
• Our observations suggest a novel mechanism whereby subunit specific changes in the NMDA receptor complex may be linked to chronic anxiety in AD via effects on GlyRS function. (PMID:17433503)
• NR2A(F637) influences NMDA receptor affinity, ion channel gating, and ethanol sensitivity; the changes in NMDA receptor affinity are likely to be the result of altered ion channel gating (PMID:17519952)
• NR2A and NR2B receptor gene variations modify age at onset in Huntington disease in a sex-specific manner. (PMID:17569088)
• NMDAR2A is commonly hypermethylated in primary human colorectal carcinoma and possesses tumor-suppressive activity. (PMID:17922030)
• laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. (PMID:17942280)
• The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G(1) phase. (PMID:18178157)
• This study found that the NR2A protein level significationalty elevated in pateint with deression. (PMID:18570704)
• NR1-1a (D732E)/NR2A and NR1-1a (D723A)/NR2A trafficked as efficiently as NR1-1a/NR2A, there was a 90% decrease in surface expression for NR1-1a (D732A)/NR2A. (PMID:18990687)
• Data show that expression of NMDA receptor NR1, NR2A, and NR2B subunits is significantly lower in brains of cirrhotic alcoholics than in the corresponding areas in both controls and alcoholics without co-morbid disease. (PMID:18991843)
• SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression. (PMID:19088076)
• Tyrosine-1325 phosphorylation regulates N-methyl-D-aspartate (NMDA) receptor channel properties and NMDA receptor-mediated downstream signaling to modulate depression-related behavior. (PMID:19834457)
• Functional (GT)n polymorphisms in promoter region of N-methyl-d-aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumes (PMID:20070378)
• the PFC, glutamatergic regulation of PV-containing inhibitory neurons via NR2A-containing NMDA receptors does not appear to be altered in bipolar disorder. (PMID:20148871)
• Data demonstrate that tat treatment of human neurons results in tyrosine phosphorylation of the NMDAR subunit 2A (NR2A) in a src kinase-dependent manner. (PMID:20448061)
• NMDA subunit NR2A is not involved in amygdala hyperexcitability of patients with temporal lobe epilepsy. (PMID:20848605)
• Mutations cause mental neurodevvelopmental disordes such as epilepsy and mental retardation. (PMID:20890276)
• Data show that that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B) are expressed in astrocytes, but at different levels. (PMID:21152063)
• This review focuses on the role of the NMDA receptor subunits in schizophrenia, particularly via altering the balance of NR2 subunits during early development, could influence NRG1 signalling {REVIEW} (PMID:21371516)
• Exome sequencing identifies GRIN2A as frequently mutated in melanoma. (PMID:21499247)
• In melanoma, GRIN2A is identified as a common somatic mutation. (PMID:21499247)
• The results show a significant association between polymorphism of the GRIN2A gene and alcoholism. (PMID:21507155)
• glutamate receptor gene GRIN2A is a Parkinson’s disease modifier gene via interaction with coffee (PMID:21876681)
• identified as prime candidate gene for photoparoxysmal response (PMID:21883175)
• Polymorphism rs11866328 in the GRIN2A gene might be a genetic variant underlying the susceptibility of HBV carriers to disease progression. (PMID:22004137)
• After 7 days of chronic alcohol exposure there are significant increases in mRNA expression of GRIN2A in cultured neurons derived from alcoholic subjects, but not in cultures from nonalcoholics. (PMID:22486492)

Cross-species orthologs

36 orthologs

Organism	Symbol	Gene ID
danio_rerio	grin2aa	ENSDARG00000034493
danio_rerio	grin2ab	ENSDARG00000070543
mus_musculus	Grin2a	ENSMUSG00000059003
rattus_norvegicus	Grin2a	ENSRNOG00000033942
drosophila_melanogaster	GluRIIA	FBGN0004620
drosophila_melanogaster	GluRIIB	FBGN0020429
drosophila_melanogaster	clumsy	FBGN0026255
drosophila_melanogaster	GluRIID	FBGN0028422
drosophila_melanogaster	Ir7b	FBGN0029965
drosophila_melanogaster	Ir7c	FBGN0029966
drosophila_melanogaster	Ir7g	FBGN0029968
drosophila_melanogaster	Ir25a	FBGN0031634
drosophila_melanogaster	Ir60a	FBGN0034994
drosophila_melanogaster	Ir64a	FBGN0035604
drosophila_melanogaster	Ir68a	FBGN0036150
drosophila_melanogaster	Ir75a	FBGN0036757
drosophila_melanogaster	Ir75d	FBGN0036829
drosophila_melanogaster	Ir76b	FBGN0036937
drosophila_melanogaster	Ir84a	FBGN0037501
drosophila_melanogaster	Ir85a	FBGN0037630
drosophila_melanogaster	Ir92a	FBGN0038789
drosophila_melanogaster	Grik	FBGN0038840
drosophila_melanogaster	Ir41a	FBGN0040849
drosophila_melanogaster	GluRIIC	FBGN0046113
drosophila_melanogaster	GluRIIE	FBGN0051201
drosophila_melanogaster	Nmdar2	FBGN0053513
drosophila_melanogaster	Ir7e	FBGN0259189
drosophila_melanogaster	Ir94d	FBGN0259193
drosophila_melanogaster	Ir93a	FBGN0259215
drosophila_melanogaster	Ir40a	FBGN0259683
drosophila_melanogaster	Ir76a	FBGN0260874
drosophila_melanogaster	Ir75c	FBGN0261401
drosophila_melanogaster	Ir75b	FBGN0261402
caenorhabditis_elegans		WBGENE00001618
caenorhabditis_elegans		WBGENE00003775
caenorhabditis_elegans		WBGENE00012190

Paralogs (17): GRIN2D (ENSG00000105464), GRIK5 (ENSG00000105737), GRIN3B (ENSG00000116032), GRIA2 (ENSG00000120251), GRIA3 (ENSG00000125675), GRIK4 (ENSG00000149403), GRID2 (ENSG00000152208), GRIA4 (ENSG00000152578), GRIA1 (ENSG00000155511), GRIN2C (ENSG00000161509), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, NMDA 2A — Q12879 (reviewed: Q12879)

Alternative names: Glutamate [NMDA] receptor subunit epsilon-1, N-methyl D-aspartate receptor subtype 2A

All UniProt accessions (9): A0A1B0GU35, A0A1B0GUT1, A0A1B0GVW1, A0A6Q8PGD2, A0A6Q8PHM7, A0A890YTL4, Q12879, F5GZ52, Q547U9

UniProt curated annotations — full annotation on UniProt →

Function. Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium. Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators. Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte.

Subunit / interactions. Heterotetramer. Forms heterotetrameric channels composed of two GluN1/zeta subunits (GRIN1), and two identical GluN2/epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) or GluN3 subunits (GRIN3A or GRIN3B) (in vitro). Can also form heterotetrameric channels that contain at least two GluN1 subunits and at least two different GluN2 subunits (or a combination of one GluN2 and one GluN3 subunits) (in vitro). In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB. Found in a complex with GRIN1 and GRIN3B. Interacts with AIP1. Interacts with HIP1 and NETO1. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes. Interacts with PDZ domains of PATJ and DLG4. Interacts with LRFN2. Interacts with RPH3A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes. Interacts with SORCS2. Interacts with ARC; preventing ARC oligomerization. Interacts (via the extreme C-terminus) with FRMPD2 (the second PDZ domain); the interaction is direct and is likely to promote NMDAR-mediated neural signal transmission. GRIN2A binds FRMPD2 with lower affinity than GRIN2B.

Subcellular location. Cell projection. Dendritic spine. Cell membrane. Synapse. Postsynaptic cell membrane. Cytoplasmic vesicle membrane.

Disease relevance. Epilepsy, focal, with speech disorder and with or without impaired intellectual development (FESD) [MIM:245570] An autosomal dominant, highly variable neurologic disorder. Features range from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and intellectual disability to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, intellectual disability and speech dyspraxia, and benign epilepsy with centrotemporal spikes. The disease is caused by variants affecting the gene represented in this entry. Rare genetic variations in GRIN2A may be associated with susceptibility to schizophrenia, a severe psychiatric disorder characterized by hallucinations, delusions, disorganized speech and behavior, cognitive impairment, and social withdrawal. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.

Activity regulation. NMDA glutamate receptor activity is inhibited by endogenous Mg(2+) in a voltage-dependent manner. NMDA glutamate receptor activity is inhibited by endogenous Zn(2+). NMDA glutamate receptor activity is inhibited by endogenous protons.

Domain organisation. Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand-binding domains triggers channel gating. A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12879-1	1	yes
Q12879-2	2

RefSeq proteins (3): NP_000824, NP_001127879, NP_001127880 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001320	Iontro_rcpt_C	Domain
IPR001508	Iono_Glu_rcpt_met	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR015683	Ionotropic_Glu_rcpt	Family
IPR018884	NMDAR2_C	Domain
IPR019594	Glu/Gly-bd	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily

Pfam: PF00060, PF01094, PF10565, PF10613

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (259 total): sequence variant 129, strand 36, helix 30, binding site 10, mutagenesis site 8, modified residue 8, glycosylation site 7, topological domain 5, compositionally biased region 5, turn 5, disulfide bond 4, region of interest 3, transmembrane region 3, signal peptide 1, chain 1, short sequence motif 1, site 1, intramembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5H8F	X-RAY DIFFRACTION	1.81
5H8Q	X-RAY DIFFRACTION	1.9
3NFL	X-RAY DIFFRACTION	1.91
9MUM	X-RAY DIFFRACTION	1.97
5KCJ	X-RAY DIFFRACTION	2.09
5I2N	X-RAY DIFFRACTION	2.12
5H8H	X-RAY DIFFRACTION	2.23
5TP9	X-RAY DIFFRACTION	2.4
9MUL	X-RAY DIFFRACTION	2.4
5KDT	X-RAY DIFFRACTION	2.44
5TPA	X-RAY DIFFRACTION	2.48
5H8N	X-RAY DIFFRACTION	2.5
5I2K	X-RAY DIFFRACTION	2.86
7EU7	ELECTRON MICROSCOPY	3.5
8VUT	ELECTRON MICROSCOPY	3.7
8JJ1	ELECTRON MICROSCOPY	3.77
7EOT	ELECTRON MICROSCOPY	3.8
8JIZ	ELECTRON MICROSCOPY	3.8
8VUL	ELECTRON MICROSCOPY	3.83
8VUR	ELECTRON MICROSCOPY	3.84
8VUQ	ELECTRON MICROSCOPY	3.85
7EOS	ELECTRON MICROSCOPY	3.9
8VUJ	ELECTRON MICROSCOPY	3.92
8VUS	ELECTRON MICROSCOPY	3.99
7EOR	ELECTRON MICROSCOPY	4
8VUN	ELECTRON MICROSCOPY	4.01
7EOQ	ELECTRON MICROSCOPY	4.1
8E99	ELECTRON MICROSCOPY	4.24
7EOU	ELECTRON MICROSCOPY	4.3
8JJ2	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12879-F1	60.70	0.18

Antibody-complex structures (SAbDab): 13 — 8E99, 8JIZ, 8JJ0, 8JJ1, 8JJ2, 8VUH, 8VUJ, 8VUL, 8VUN, 8VUQ, 8VUR, 8VUS, 8VUT

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 614 (functional determinant of nmda receptors)

Ligand- & substrate-binding residues (10): 44; 128; 266; 282; 511; 513; 518; 689; 690; 731

Post-translational modifications (8): 882, 890, 929, 1025, 1059, 1062, 1198, 1291

Disulfide bonds (4): 87–320, 429–455, 436–456, 745–800

Glycosylation sites (7): 75, 340, 380, 443, 444, 541, 687

Mutagenesis-validated functional residues (8):

Position	Phenotype
552	changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
552	changed glutamate-gated calcium ion channel activity characterized by accelerated response activation time and increased
552	changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay
552	no effect on localization to the cell membrane. changed glutamate-gated calcium ion channel activity characterized by in
552	no effect on localization to the cell membrane. changed glutamate-gated calcium ion channel activity characterized by de
632	no effect on localization to the cell membrane. no effect on agonist potency and channel activation by glutamate and gly
646	no effect on localization to the cell membrane. results in increased glycine potency and channel activation at lower ago

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-6794361	Neurexins and neuroligins
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 485 (showing top): GOBP_MEMORY, RNGTGGGC_UNKNOWN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, AAGCAAT_MIR137, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR, PAX4_01, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_RESPONSE_TO_AMINE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC

GO Biological Process (44): startle response (GO:0001964), response to amphetamine (GO:0001975), glutamate receptor signaling pathway (GO:0007215), chemical synaptic transmission (GO:0007268), brain development (GO:0007420), learning or memory (GO:0007611), memory (GO:0007613), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), response to wounding (GO:0009611), sensory perception of pain (GO:0019233), neurogenesis (GO:0022008), protein catabolic process (GO:0030163), sleep (GO:0030431), directional locomotion (GO:0033058), ionotropic glutamate receptor signaling pathway (GO:0035235), synaptic transmission, glutamatergic (GO:0035249), sodium ion transmembrane transport (GO:0035725), negative regulation of protein catabolic process (GO:0042177), dopamine metabolic process (GO:0042417), serotonin metabolic process (GO:0042428), positive regulation of apoptotic process (GO:0043065), response to ethanol (GO:0045471), regulation of synaptic plasticity (GO:0048167), regulation of neuronal synaptic plasticity (GO:0048168), positive regulation of synaptic transmission, glutamatergic (GO:0051968), excitatory postsynaptic potential (GO:0060079), long-term synaptic potentiation (GO:0060291), calcium ion transmembrane transport (GO:0070588), calcium ion transmembrane import into cytosol (GO:0097553), monoatomic cation transmembrane transport (GO:0098655), excitatory chemical synaptic transmission (GO:0098976), protein localization to postsynaptic membrane (GO:1903539), regulation of monoatomic cation transmembrane transport (GO:1904062), positive regulation of excitatory postsynaptic potential (GO:2000463), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), learning (GO:0007612), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), NMDA glutamate receptor activity (GO:0004972), zinc ion binding (GO:0008270), glutamate-gated calcium ion channel activity (GO:0022849), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), calcium channel activity (GO:0005262), protein binding (GO:0005515), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872)

GO Cellular Component (20): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), cell surface (GO:0009986), postsynaptic density (GO:0014069), NMDA selective glutamate receptor complex (GO:0017146), cytoplasmic vesicle membrane (GO:0030659), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), synaptic membrane (GO:0097060), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
Protein-protein interactions at synapses	2
Transcriptional Regulation by MECP2	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
glutamate-gated receptor activity	3
synapse	3
monoatomic ion channel activity	2
presynapse	2
synaptic membrane	2
postsynapse	2
cytoplasm	2
response to external stimulus	1
neuromuscular process	1
response to amine	1
cell surface receptor signaling pathway	1
glutamate receptor activity	1
anterograde trans-synaptic signaling	1
central nervous system development	1
animal organ development	1
head development	1
behavior	1
cognition	1
learning or memory	1
visual behavior	1
associative learning	1
response to chemical	1
response to stress	1
sensory perception	1
nervous system development	1
cell differentiation	1
macromolecule catabolic process	1
protein metabolic process	1
multicellular organismal process	1
locomotion	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
chemical synaptic transmission	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1

Protein interactions and networks

STRING

2858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIN2A	DLG4	P78352	998
GRIN2A	DLG3	Q92796	995
GRIN2A	DLG2	Q15700	992
GRIN2A	GRIN1	P35437	990
GRIN2A	GRIN3B	O60391	988
GRIN2A	GRIN3A	Q8TCU5	988
GRIN2A	GRIN2D	O15399	984
GRIN2A	GRIN2C	Q14957	983
GRIN2A	GRIN2B	Q13224	983
GRIN2A	FYN	P06241	932
GRIN2A	GRM3	Q14832	924
GRIN2A	DLG1	Q12959	923
GRIN2A	CAMK2A	Q9UQM7	919
GRIN2A	SRC	P12931	886
GRIN2A	ADCY8	P40145	829

IntAct

152 interactions, top by confidence:

A	B	Type	Score
DLG4	GRIN2A	psi-mi:“MI:0915”(physical association)	0.810
GRIN2A	DLG4	psi-mi:“MI:0915”(physical association)	0.810
DLG4	GRIN2A	psi-mi:“MI:0407”(direct interaction)	0.810
GRIN2A	DLG4	psi-mi:“MI:0407”(direct interaction)	0.810
NOS1	GRIN2A	psi-mi:“MI:0915”(physical association)	0.610
GRIN2A	NOS1	psi-mi:“MI:0407”(direct interaction)	0.610
GRIN2A	Dlg3	psi-mi:“MI:0407”(direct interaction)	0.560
Dlg4	GRIN2A	psi-mi:“MI:0407”(direct interaction)	0.560
Dlg3	GRIN2A	psi-mi:“MI:0407”(direct interaction)	0.560
GRIN2A	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.560
Ptpn4	GRIN2A	psi-mi:“MI:0915”(physical association)	0.520
GRIN2A	Ptpn4	psi-mi:“MI:0915”(physical association)	0.520
GRIN2A	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2A	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2A	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2A	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2A	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIN2A	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	GRIN2A	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (136): GRIN2A (Two-hybrid), GRIN1 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG1 (Affinity Capture-Western), GRIN2A (Reconstituted Complex), GRIN2A (Affinity Capture-Western), GRIN2A (Affinity Capture-Western), GRIN2A (Affinity Capture-MS), GRIN2A (Affinity Capture-MS), GRIN2A (Affinity Capture-Western), GRIN2A (Affinity Capture-Western), GRIN2A (Affinity Capture-Western), DLG4 (Two-hybrid), DLG4 (Reconstituted Complex), APLP1 (Affinity Capture-Western)

ESM2 similar proteins: A7XY94, B3LZ39, B3P2E5, B4GF83, B4I414, B4JHV0, B4KD90, B4LZB5, B4MU83, B4PVB0, B4QWW7, B7ZSK1, P19490, P19491, P19492, P19493, P22756, P23818, P23819, P31424, P35436, P39086, P41594, P42261, P42262, P42263, P48058, P58421, Q00959, Q00960, Q01097, Q03445, Q12879, Q13224, Q24418, Q296F7, Q38PU4, Q38PU5, Q38PU6, Q38PU7

Diamond homologs: A0A2R8QF68, A7XY94, B1AS29, E9NA96, P19439, P19490, P19491, P19492, P19493, P20262, P22756, P23818, P23819, P26591, P34299, P35436, P39086, P39087, P42260, P42261, P42262, P42263, P42264, P48058, Q00959, Q01812, Q03445, Q10914, Q12879, Q13002, Q13003, Q16099, Q16478, Q21415, Q38PU2, Q38PU3, Q38PU4, Q38PU5, Q38PU6, Q38PU7

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
FYN	up-regulates	GRIN2A	phosphorylation
SRC	up-regulates	GRIN2A	phosphorylation
GRIN2A	“up-regulates quantity”	calcium(2+)	relocalization
GRIN2A	“form complex”	“NMDA receptor_2A”	binding
DLG4	“up-regulates activity”	GRIN2A	relocalization
PTPN5	“down-regulates activity”	GRIN2A	dephosphorylation
DYRK1A	“up-regulates quantity”	GRIN2A	phosphorylation
PRKCA	unknown	GRIN2A	phosphorylation
CDK5	“up-regulates activity”	GRIN2A	phosphorylation
FYN	“up-regulates activity”	GRIN2A	phosphorylation
SRC	“up-regulates activity”	GRIN2A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	47.6×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	45.3×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	45.3×	4e-06
Long-term potentiation	5	39.6×	6e-06
Assembly and cell surface presentation of NMDA receptors	9	38.1×	2e-10
Neurexins and neuroligins	10	32.8×	1e-10
Protein-protein interactions at synapses	6	26.6×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	74.3×	7e-16
protein localization to synapse	6	53.4×	2e-07
receptor clustering	7	50.8×	2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	34.6×	2e-06
protein-containing complex assembly	9	11.9×	5e-06
cell-cell adhesion	10	11.8×	2e-06
chemical synaptic transmission	7	6.3×	4e-03
intracellular signal transduction	9	4.0×	1e-02

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — BLCA, CHOL, COADREAD, MT, PANCREAS.

Clinical variants and AI predictions

ClinVar

2441 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	154
Likely pathogenic	137
Uncertain significance	959
Likely benign	734
Benign	149

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028882	NM_001134407.3(GRIN2A):c.593G>A (p.Trp198Ter)	Pathogenic
1041575	NM_001134407.3(GRIN2A):c.2289T>G (p.Ile763Met)	Pathogenic
1068346	NM_001134407.3(GRIN2A):c.1497+2T>C	Pathogenic
1069106	NM_001134407.3(GRIN2A):c.2833_2834insTTCAG (p.Asp945fs)	Pathogenic
1069297	NM_001134407.3(GRIN2A):c.812_813del (p.Glu271fs)	Pathogenic
1069306	NM_001134407.3(GRIN2A):c.1827G>A (p.Trp609Ter)	Pathogenic
1071858	NC_000016.9:g.(?9916111)(9916291_?)del	Pathogenic
1071859	NC_000016.9:g.(?10273845)(10274268_?)del	Pathogenic
1073743	NC_000016.9:g.(?9857006)(9862956_?)del	Pathogenic
1073744	NC_000016.9:g.(?9916101)(9923529_?)dup	Pathogenic
1073902	NM_001134407.3(GRIN2A):c.460C>T (p.Gln154Ter)	Pathogenic
1075612	NC_000016.9:g.(?9984833)(9984967_?)del	Pathogenic
1075856	NM_001134407.3(GRIN2A):c.1134G>A (p.Trp378Ter)	Pathogenic
1076203	NM_001134407.3(GRIN2A):c.1115G>A (p.Trp372Ter)	Pathogenic
1335206	NM_001134407.3(GRIN2A):c.1817G>A (p.Trp606Ter)	Pathogenic
1335965	NM_001134407.3(GRIN2A):c.19dup (p.Trp7fs)	Pathogenic
1347497	NM_001134407.3(GRIN2A):c.1691T>G (p.Met564Arg)	Pathogenic
1366802	NM_001134407.3(GRIN2A):c.1425C>G (p.Tyr475Ter)	Pathogenic
1407756	NM_001134407.3(GRIN2A):c.1702del (p.Val568fs)	Pathogenic
1413913	NM_001134407.3(GRIN2A):c.645del (p.Gln216fs)	Pathogenic
1451688	NM_001134407.3(GRIN2A):c.1194del (p.Cys399fs)	Pathogenic
1453886	NM_001134407.3(GRIN2A):c.1831C>A (p.Leu611Met)	Pathogenic
1454126	NM_001134407.3(GRIN2A):c.3693dup (p.Ser1232fs)	Pathogenic
1457680	NC_000016.9:g.(?9934484)(9934981_?)del	Pathogenic
1459339	NC_000016.9:g.(?9857006)(10032428_?)del	Pathogenic
1459968	NC_000016.9:g.(?9857006)(10274268_?)del	Pathogenic
1468112	NM_001134407.3(GRIN2A):c.1651+2T>A	Pathogenic
1526500	GRCh37/hg19 16p13.2(chr16:9937979-10149238)	Pathogenic
1684548	GRCh37/hg19 16p13.2(chr16:10031605-10033175)x1	Pathogenic
1685865	NM_001134407.3(GRIN2A):c.4320del (p.Thr1441fs)	Pathogenic

SpliceAI

3653 predictions. Top by Δscore:

Variant	Effect	Δscore
16:10179992:CCTTA:C	donor_loss	1.0000
16:10179993:CTTAC:C	donor_loss	1.0000
16:10179994:TTA:T	donor_loss	1.0000
16:10179995:TACCT:T	donor_loss	1.0000
16:10179996:A:C	donor_loss	1.0000
16:10179997:C:CG	donor_loss	1.0000
16:10181872:CGTA:C	donor_loss	1.0000
16:10181873:GTAC:G	donor_loss	1.0000
16:10181874:TA:T	donor_loss	1.0000
16:10181875:A:AT	donor_loss	1.0000
16:10182063:GGGCT:G	acceptor_gain	1.0000
16:10182064:GGCT:G	acceptor_gain	1.0000
16:10182066:CT:C	acceptor_gain	1.0000
16:10182068:C:CC	acceptor_gain	1.0000
16:10182069:T:C	acceptor_loss	1.0000
16:10182077:C:CT	acceptor_gain	1.0000
16:10182078:G:T	acceptor_gain	1.0000
16:10182650:TCACC:T	donor_loss	1.0000
16:10182651:CAC:C	donor_loss	1.0000
16:10182652:A:AC	donor_gain	1.0000
16:10182652:ACCGC:A	donor_loss	1.0000
16:10182653:C:CC	donor_gain	1.0000
16:10182653:CCG:C	donor_gain	1.0000
16:10182653:CCGCA:C	donor_gain	1.0000
16:9764946:GCCC:G	acceptor_loss	1.0000
16:9764947:CCCTG:C	acceptor_loss	1.0000
16:9764949:CT:C	acceptor_loss	1.0000
16:9768850:CCCTG:C	donor_gain	1.0000
16:9768916:T:TA	donor_gain	1.0000
16:9798272:CTTA:C	donor_loss	1.0000

AlphaMissense

9800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:10180152:C:T	C87Y	1.000
16:9768854:G:C	S864R	1.000
16:9768854:G:T	S864R	1.000
16:9768856:T:G	S864R	1.000
16:9768953:G:C	S831R	1.000
16:9768953:G:T	S831R	1.000
16:9768955:T:G	S831R	1.000
16:9768975:A:G	L824P	1.000
16:9768975:A:T	L824Q	1.000
16:9768983:G:C	F821L	1.000
16:9768983:G:T	F821L	1.000
16:9768985:A:G	F821L	1.000
16:9768990:C:T	G819D	1.000
16:9768991:C:A	G819C	1.000
16:9768991:C:G	G819R	1.000
16:9768995:C:A	M817I	1.000
16:9768995:C:G	M817I	1.000
16:9768995:C:T	M817I	1.000
16:9768998:G:C	N816K	1.000
16:9768998:G:T	N816K	1.000
16:9769011:A:C	L812R	1.000
16:9769011:A:G	L812P	1.000
16:9769011:A:T	L812Q	1.000
16:9769046:G:C	C800W	1.000
16:9769047:C:A	C800F	1.000
16:9769047:C:G	C800S	1.000
16:9769047:C:T	C800Y	1.000
16:9769048:A:C	C800G	1.000
16:9769048:A:G	C800R	1.000
16:9769048:A:T	C800S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001052 (16:10034246 C>T), RS1000012159 (16:10039950 AG>A), RS1000024832 (16:10123806 C>A,T), RS1000027351 (16:9807126 C>A), RS1000030828 (16:9880412 A>C), RS1000032690 (16:9860227 G>A), RS1000042419 (16:10047205 T>C), RS1000053136 (16:9963472 C>T), RS1000059645 (16:10075375 G>A), RS1000061750 (16:9986636 G>A,C), RS1000063194 (16:9975321 C>A,T), RS1000066762 (16:10115335 G>A,C), RS1000070383 (16:9944364 T>A), RS1000071772 (16:9835196 G>C), RS1000072085 (16:10034027 G>A)

Disease associations

OMIM: gene MIM:138253 | disease phenotypes: MIM:117100, MIM:615502, MIM:189800, MIM:245570, MIM:613971, MIM:600512

GenCC curated gene-disease

Disease	Classification	Inheritance
Landau-Kleffner syndrome	Definitive	Autosomal dominant
complex neurodevelopmental disorder	Definitive	Autosomal dominant
early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation	Strong	Autosomal dominant
rolandic epilepsy-speech dyspraxia syndrome	Supportive	Autosomal dominant
self-limited epilepsy with centrotemporal spikes	Supportive	Autosomal dominant
continuous spikes and waves during sleep	Supportive	Autosomal dominant
developmental and epileptic encephalopathy	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (19): Landau-Kleffner syndrome (MONDO:0009509), GRIN2A-related complex neurodevelopmental disorder (MONDO:1060139), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), vascular dementia (MONDO:0004648), complex neurodevelopmental disorder (MONDO:0100038), CTCF-related neurodevelopmental disorder (MONDO:0014213), epilepsy (MONDO:0005027), preeclampsia (MONDO:0005081), focal epilepsy (MONDO:0005384), early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation (MONDO:0017325), autism spectrum disorder (MONDO:0005258), pyridoxine-dependent epilepsy (MONDO:0009945), microcephaly (MONDO:0001149)

Orphanet (11): Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Developmental and epileptic encephalopathy with spike-wave activation in sleep (Orphanet:725), Landau-Kleffner syndrome (Orphanet:98818), Non-specific syndromic intellectual disability (Orphanet:528084), CTCF-related neurodevelopmental disorder (Orphanet:363611), Preeclampsia (Orphanet:275555), Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation (Orphanet:289266), Pyridoxine-dependent-developmental and epileptic encephalopathy (Orphanet:3006), Epilepsy with auditory features (Orphanet:101046), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

109 total (30 of 109 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001276	Hypertonia
HP:0001326	EEG with irregular generalized spike and wave complexes
HP:0001328	Specific learning disability
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001345	Psychotic mentation
HP:0001350	Slurred speech
HP:0001518	Small for gestational age
HP:0001611	Hypernasal speech
HP:0001761	Pes cavus
HP:0001999	Abnormal facial shape
HP:0002066	Gait ataxia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002076	Migraine

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST001257_1	Hepatitis B	2.000000e-08
GCST001859_38	Thiazide-induced adverse metabolic effects in hypertensive patients	4.000000e-06
GCST001877_43	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	7.000000e-06
GCST002539_80	Schizophrenia	1.000000e-08
GCST002597_5	Laryngeal squamous cell carcinoma	4.000000e-07
GCST002938_6	Copper levels	7.000000e-07
GCST003140_2	Chronic kidney disease	5.000000e-06
GCST003542_209	Night sleep phenotypes	9.000000e-06
GCST004502_2	Waist circumference adjusted for BMI (smoking interaction)	2.000000e-06
GCST004521_136	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004946_47	Schizophrenia	3.000000e-09
GCST005790_38	Rosacea symptom severity	7.000000e-06
GCST006073_14	Tenofovir clearance in HIV infection	8.000000e-06
GCST006803_79	Schizophrenia	6.000000e-09
GCST007201_200	Schizophrenia	2.000000e-08
GCST007201_226	Schizophrenia	6.000000e-09
GCST007325_99	General risk tolerance (MTAG)	2.000000e-10
GCST007429_122	Lung function (FVC)	2.000000e-10
GCST007432_58	FEV1	3.000000e-06
GCST008103_4	Bipolar disorder	1.000000e-10
GCST008115_47	Bipolar I disorder	5.000000e-07
GCST008595_99	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	4.000000e-09
GCST009391_1984	Metabolite levels	3.000000e-06
GCST009600_87	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-10
GCST009846_17	Hallux valgus	3.000000e-06
GCST010002_109	Refractive error	1.000000e-17
GCST011102_18	Bipolar disorder	9.000000e-11
GCST011494_69	Daytime nap	2.000000e-09
GCST012277_5	Clostridioides difficle infection	8.000000e-07
GCST012465_53	Bipolar disorder	2.000000e-08

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0009180	rosacea severity measurement
EFO:0008579	risk-taking behaviour
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0009963	bipolar I disorder
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0005058	tyrosine measurement
EFO:0007828	daytime rest measurement
EFO:0009130	clostridium difficile infection
EFO:0005943	response to bevacizumab

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D004828	Epilepsies, Partial	C10.228.140.490.360
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D018887	Landau-Kleffner Syndrome	C10.228.140.490.493.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D011225	Pre-Eclampsia	C12.050.703.395.249
C536254	Pyridoxine-dependent epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1907604 (PROTEIN COMPLEX), CHEMBL1972 (SINGLE PROTEIN), CHEMBL2094124 (PROTEIN COMPLEX GROUP), CHEMBL5483086 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

37 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,435,444 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1699	MEMANTINE HYDROCHLORIDE	4	8,827
CHEMBL395091	ESKETAMINE	4	958
CHEMBL52440	DEXTROMETHORPHAN	4	33,223
CHEMBL55	PENTAMIDINE	4	27,049
CHEMBL660	AMANTADINE	4	69,750
CHEMBL742	KETAMINE	4	101,983
CHEMBL771	CYCLOSERINE	4	23,487
CHEMBL807	MEMANTINE	4	34,597
CHEMBL95	TACRINE	4	35,360
CHEMBL592	LEVORPHANOL	4	75,131
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL86715	PROCYCLIDINE	4	5,456
CHEMBL900	ORPHENADRINE	4	8,087
CHEMBL350719	ESMETHADONE	3	26,004
CHEMBL5095095	DALZANEMDOR	3	20
CHEMBL589390	LATREPIRDINE	3	466
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL1165411	DEXOXADROL	2	1,278
CHEMBL1254766	DEXTRORPHAN	2	6,521
CHEMBL159659	LEVOMETHADONE	2	1,664
CHEMBL159660	ALPHAMETHADOL	2
CHEMBL162243	BETAMETHADOL	2
CHEMBL2106325	DIMEMORFAN	2
CHEMBL275528	PHENCYCLIDINE	2
CHEMBL284237	DIZOCILPINE	2
CHEMBL305904	ETOXADROL	2
CHEMBL305187	IFENPRODIL	2
CHEMBL14935	TEZAMPANEL ANHYDROUS	2
CHEMBL17350	TRAXOPRODIL	2
CHEMBL182066	RADIPRODIL	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2229193	GRIN2A		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Ionotropic glutamate receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
NYX-2925	Positive	10.26	pEC50
SAGE-718	Positive	7.07	pEC50
TCN-201	Negative	7.0	pIC50
plazinemdor	Positive	6.36	pEC50
TCN-213	Negative	6.26	pIC50

Binding affinities (BindingDB)

271 measured of 307 human assays (307 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[[(3,4-difluorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	16.2 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	19.6 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
cis-(1R,2R)-2-[2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-7-fluoro-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	21 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
(1R,2R)-2-[2-[[5-chloro-3- (trifluoromethyl)pyrazol-1- yl]methyl]-4-oxo-pyrido[1,2- a]pyrimidin-6- yl]cyclopropanecarbonitrile	EC50	24 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
cis-(1R,2R)-2-[7-chloro-2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	36.8 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
cis-(1R,2R)-2-[2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-8-methyl-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	39 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chlorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	39.5 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	61 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
cis-(1R,2R)-2-[2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-7-methyl-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	77 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
cis-(1R,2R)-2-[2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-7-methoxy-4-oxopyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	79 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-6-ethyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	87.8 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
2-((3,5-dichloro-1H-pyrazol-1- yl)methyl)-7-methoxy-6-(2- methylcyclopropyl)-4H-pyrido[1,2- a]pyrimidin-4-one	EC50	102 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(4-methyl-3-pyridinyl)methyl]pyrazine-2-carboxamide	IC50	108 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
6-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(1-methylimidazol-2-yl)methyl]pyridine-3-carboxamide	IC50	108 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
cis-(1R,2R)-2-[2-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-8-(trifluoromethyl)pyrido[1,2-a]pyrimidin-6-yl]cyclopropane-1-carbonitrile	EC50	123 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
2-[[5-chloro-3- (trifluoromethyl)pyrazol-1- yl]methyl]-6-[(1R,2R)-2- (hydroxymethyl)cyclopropyl]-7- methyl-pyrido[1,2-a]pyrimidin-4-one	EC50	126 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(4-fluorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	137 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]-6-(trifluoromethyl)pyrazine-2-carboxamide	IC50	169 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
2-[2-[[3-chloro-5- (trifluoromethyl)pyrazol-1- yl]methyl]-7-fluoro-4-oxo-pyrido[1,2- a]pyrimidin-6- yl]cyclopropanecarbonitrile	EC50	178 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[1-(2-methyl-1,3-thiazol-5-yl)ethyl]pyrazine-2-carboxamide	IC50	180 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(4-methyl-3-pyridinyl)methyl]pyridine-2-carboxamide	IC50	187 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyridine-2-carboxamide	IC50	204 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3,4-difluorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyridine-2-carboxamide	IC50	219 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
(1R,2R)-2-(2-((3,5-dichloro-1H- pyrazol-1-yl)methyl)-8-methyl-4-oxo- 4H-pyrido[1,2-a]pyrimidin-6- yl)cyclopropanecarbonitrile	EC50	222 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
2-[2-[[3-chloro-5- (trifluoromethyl)pyrazol-1- yl]methyl]-7-methyl-4-oxo- pyrido[1,2-a]pyrimidin-6- yl]cyclopropanecarbonitrile	EC50	227 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
2-[2-[[3-chloro-5- (trifluoromethyl)pyrazol-1- yl]methyl]-8-methyl-4-oxo- pyrido[1,2-a]pyrimidin-6- yl]cyclopropanecarbonitrile	EC50	269 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3,4-difluorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	313 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(1,3-thiazol-5-ylmethyl)pyridine-2-carboxamide	IC50	347 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3,5-difluorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	366 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
2-[(N-ethyl-4-fluoro-anilino)methyl]- 6-(2-furyl)pyrido[1,2-a]pyrimidin-4- one	EC50	371 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(pyridin-3-ylmethyl)pyrazine-2-carboxamide	IC50	439 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3,4-dichlorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	494 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrazine-2-carboxamide	IC50	624 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
6-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(5-methylpyrazin-2-yl)methyl]pyridine-3-carboxamide	IC50	630 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(1,5-dimethylpyrrol-2-yl)methyl]pyrazine-2-carboxamide	IC50	757 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(pyridin-3-ylmethyl)pyridine-2-carboxamide	IC50	758 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
6-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(pyrazin-2-ylmethyl)pyridine-3-carboxamide	IC50	790 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
(S)-2-(2-Adamantan-1-yl-acetylamino)-N-{3-[4-(3-amino-propylamino)-butylamino]-propyl}-3-cyclohexyl-propionamide	IC50	794 nM
5-[[(3-chlorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	839 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(2-methoxy-4-pyridinyl)methyl]pyrazine-2-carboxamide	IC50	850 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(1,3-thiazol-5-ylmethyl)pyrazine-2-carboxamide	IC50	929 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
(1S,2S)-2-[2-[[5-chloro-3- (trifluoromethyl)pyrazol-1- yl]methyl]-8-methyl-4-oxo- pyrido[1,2-a]pyrimidin-6- yl]cyclopropanecarbonitrile	EC50	951 nM	US-10280165: Pyridopyrimidinones and methods of use thereof
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyridine-2-carboxamide	IC50	1020 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(4-chloro-3-fluorophenyl)sulfonylamino]methyl]-6-methyl-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyrazine-2-carboxamide	IC50	1020 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chlorophenyl)sulfonylamino]methyl]-N-[(2-methyl-1,3-thiazol-5-yl)methyl]pyridine-2-carboxamide	IC50	1040 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(5-fluoro-3-pyridinyl)methyl]pyrazine-2-carboxamide	IC50	1100 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-[(5-methylpyrazin-2-yl)methyl]pyrazine-2-carboxamide	IC50	1250 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(pyrazin-2-ylmethyl)pyridine-2-carboxamide	IC50	1690 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(pyridin-4-ylmethyl)pyrazine-2-carboxamide	IC50	1700 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A
5-[[(3-chloro-4-fluorophenyl)sulfonylamino]methyl]-N-(1,3-oxazol-5-ylmethyl)pyridine-2-carboxamide	IC50	1950 nM	US-9963434: N-arylmethyl sulfonamide negative modulators of NR2A

ChEMBL bioactivities

758 potent at pChembl≥5 of 1004 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL12513
9.30	IC50	0.5	nM	CHEMBL276708
9.10	IC50	0.8	nM	CHEMBL12513
9.02	IC50	0.95	nM	MEMANTINE
9.02	Ki	0.96	nM	CHEMBL39881
9.00	IC50	1	nM	CHEMBL12804
8.96	IC50	1.1	nM	CHEMBL274422
8.92	IC50	1.2	nM	CHEMBL12242
8.92	Ki	1.2	nM	DIZOCILPINE
8.85	Ki	1.4	nM	CHEMBL5185347
8.82	IC50	1.5	nM	CHEMBL537478
8.82	IC50	1.5	nM	CHEMBL274422
8.82	IC50	1.5	nM	CHEMBL273662
8.77	IC50	1.7	nM	CHEMBL269683
8.71	Ki	1.94	nM	CNS-5161
8.70	IC50	2	nM	CHEMBL536107
8.70	Ki	2	nM	CHEMBL299294
8.64	Ki	2.3	nM	CHEMBL39773
8.59	Ki	2.6	nM	CHEMBL290738
8.59	IC50	2.6	nM	CHEMBL450325
8.52	Ki	3	nM	CHEMBL5208012
8.52	IC50	3	nM	CHEMBL552664
8.52	Ki	3	nM	CHEMBL166935
8.52	Ki	3	nM	CHEMBL166991
8.51	Ki	3.1	nM	CHEMBL290649
8.48	Ki	3.3	nM	CHEMBL5208606
8.47	Ki	3.4	nM	CHEMBL66626
8.46	Ki	3.5	nM	CHEMBL50872
8.42	Ki	3.8	nM	CHEMBL68831
8.42	Ki	3.8	nM	CHEMBL306899
8.40	IC50	4	nM	CHEMBL363010
8.40	IC50	4	nM	BESONPRODIL
8.40	IC50	4	nM	CHEMBL317229
8.40	Ki	4	nM	CHEMBL354482
8.40	Ki	4	nM	CHEMBL170552
8.40	Ki	4	nM	CHEMBL169695
8.39	IC50	4.1	nM	CHEMBL557993
8.38	IC50	4.2	nM	CHEMBL2398522
8.38	IC50	4.2	nM	CHEMBL536107
8.36	Ki	4.4	nM	CHEMBL40730
8.36	IC50	4.4	nM	CHEMBL61720
8.35	Ki	4.5	nM	CHEMBL100656
8.33	IC50	4.7	nM	CHEMBL297881
8.31	Ki	4.9	nM	CHEMBL70918
8.30	IC50	5	nM	CHEMBL363722
8.30	Ki	5	nM	CHEMBL166697
8.29	Ki	5.1	nM	CHEMBL38994
8.25	Ki	5.6	nM	CHEMBL305195
8.23	IC50	5.9	nM	LICOSTINEL
8.22	IC50	6	nM	RADIPRODIL

PubChem BioAssay actives

623 with measured affinity, of 1742 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[7-(4-chlorophenyl)-2,3-dioxo-1,4-dihydroquinoxalin-5-yl]methylphosphonic acid	144677: Inhibitory activity against Xenopus laevis oocyte expressing 1A/2A heteromeric human NMDA (hNMDA) receptor	ic50	0.0002	uM
(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144039: Compound was tested in vitro for its inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor by using [3H]CGP-39653 binding assay	ic50	0.0005	uM
Memantine	755470: Antagonist activity at recombinant GluN1/GluN2A receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of glycine/glutamate-induced inward current at -70mV by two-electrode voltage clamp assay	ic50	0.0009	uM
(7-fluoro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0010	uM
2-[(12S)-7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0010	uM
[(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)-hydroxymethyl]phosphonic acid	144677: Inhibitory activity against Xenopus laevis oocyte expressing 1A/2A heteromeric human NMDA (hNMDA) receptor	ic50	0.0011	uM
(1S,9R)-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene	156805: The compound was tested for its ability to block PCP N-methyl-D-aspartate glutamate receptor at the PCP (phencyclidine) binding site in postmortem human frontal cortex.	ki	0.0012	uM
[hydroxy-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0012	uM
2-[(11S)-7-bromo-11-ethyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0014	uM
(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0015	uM
[(benzylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0015	uM
(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0017	uM
2-(2-chloro-5-methylsulfanylphenyl)-1-methyl-1-(3-methylsulfanylphenyl)guanidine	143453: In vitro displacement of [3H]MK-801 from N-methyl-D-aspartate glutamate receptor	ki	0.0019	uM
[(benzylamino)-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0020	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-pyridinyl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0020	uM
2-[(12S)-7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0023	uM
2-(7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0026	uM
6,7-dichloro-5-[1-(1,2,4-triazol-4-yl)propyl]-1,4-dihydroquinoxaline-2,3-dione	1859120: Displacement of [3H]L-689560 from NMDA receptor (unknown origin)	ic50	0.0026	uM
2-[(11S)-7-bromo-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0030	uM
[(cyclohexylmethylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrochloride	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0030	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)pyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0030	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-ethylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0030	uM
2-[(11S)-7-chloro-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0031	uM
2-[(11S)-7-bromo-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0033	uM
4-[3-(4-benzylpiperidin-1-yl)-2-methylpropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0034	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)quinolin-4-yl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0035	uM
4-[3-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0038	uM
4-[3-(4-benzylpiperidin-1-yl)-2-hydroxypropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0038	uM
2-(4-benzylpiperidin-1-yl)-2-oxo-N-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0040	uM
6-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3H-1,3-benzoxazol-2-one	143455: Inhibition of [3H]Ro-256981 binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0040	uM
1-[2-(4-hydroxyphenoxy)ethyl]-4-[(4-methylphenyl)methyl]piperidin-4-ol	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0040	uM
[4-amino-6-(3,4-dihydro-1H-isoquinolin-2-yl)-2-pyridinyl]methanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-methyl-4-pyridinyl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-5-methylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
[(furan-2-ylmethylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0041	uM
N,N’-bis[6-(2,2-diphenylethylamino)hexyl]dodecane-1,12-diamine	755470: Antagonist activity at recombinant GluN1/GluN2A receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of glycine/glutamate-induced inward current at -70mV by two-electrode voltage clamp assay	ic50	0.0042	uM
6,7-dichloro-5-[(1-propylimidazol-4-yl)methyl]-1,4-dihydroquinoxaline-2,3-dione	1859120: Displacement of [3H]L-689560 from NMDA receptor (unknown origin)	ic50	0.0044	uM
2-[(11S)-7-chloro-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0044	uM
(1S,9R)-10-[(2R)-2-methoxypropyl]-1,13,13-trimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-5-ol	1960006: Antagonist activity at NMDA receptor (unknown origin) assessed as inhibition constant	ki	0.0045	uM
7-chloro-6-methyl-5-nitro-1,4-dihydroquinoxaline-2,3-dione	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0047	uM
1-[(2R)-2-hydroxy-3-(4-hydroxyphenyl)propyl]-4-[(4-methylphenyl)methyl]piperidin-4-ol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0049	uM
2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0050	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-methylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0050	uM
2-(7-chloro-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0051	uM
4-[(1R,2S)-3-(4-benzylpiperidin-1-yl)-1-hydroxy-2-methylpropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0056	uM
6,7-dichloro-5-nitro-1,4-dihydroquinoxaline-2,3-dione	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0059	uM
2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-oxo-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0060	uM
(4-benzylpiperidin-1-yl)-(4,6-dihydroxy-1H-indol-2-yl)methanone	143455: Inhibition of [3H]Ro-256981 binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0060	uM
2-(7-chloro-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0066	uM
5,6,7-trichloro-4-hydroxy-3-nitroso-1H-quinolin-2-one	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0070	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression	5
Excitatory Amino Acid Agonists	affects cotreatment, decreases reaction, increases response to substance, affects binding, increases activity (+1 more)	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
mercuric bromide	affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silver	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cypermethrin	decreases expression	1
sodium arsenite	affects methylation	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
conotoxin GV	affects cotreatment, decreases activity	1
chromium hexavalent ion	increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
eprenetapopt	affects expression, affects reaction	1
Fulvestrant	increases methylation, affects cotreatment	1
Leflunomide	increases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Cyclic AMP	increases expression, affects cotreatment	1

ChEMBL screening assays

324 unique, capped per target: 296 binding, 23 functional, 4 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105653	Binding	Inhibition of dexamethasone-induced human NR1-1a/NR2A receptor-mediated excitotoxicity in (S)-glutamate/glycine-stimulated mouse L12-G10 cells assessed as LDH release after 30 mins	Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. — J Med Chem
CHEMBL1225540	Functional	Antagonist activity at wild type NR1/NR2A receptor expressed in Xenopus oocytes assessed as ratio of residual current induced by agonist in presence of compound to residual current induced by agonist alone at 10 uM by two-electrode voltage-	Identification of a novel NR2B-selective NMDA receptor antagonist using a virtual screening approach. — Bioorg Med Chem Lett
CHEMBL4680007	ADMET	Inhibition of NMDA receptor (unknown origin)	Fragment-Based Discovery of Novel Allosteric MEK1 Binders. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 2 transformed cell line, 1 spontaneously immortalized cell line, 1 embryonic stem cell, 1 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3TY	CHO-hGluN1-hGluN2A	Spontaneously immortalized cell line	Female
CVCL_C9D2	B’SYS HEK 293 NMDA NR1/NR2A	Transformed cell line	Female
CVCL_C9E4	SB Drug Discovery Inducible HEK-GluN1/2A	Transformed cell line	Female
CVCL_D0QL	GZHMCe003-A-1	Embryonic stem cell	Female
CVCL_D1SX	Abcam U-87MG GRIN2A KO	Cancer cell line	Male
CVCL_YJ61	SYSUi003-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

428 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT02904265	PHASE2/PHASE3	TERMINATED	Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT04592679	Not specified	COMPLETED	Cost-Effectiveness Analysis of a Rehabilitation Protocol With FES Cycling in Persons With Complete SCI
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability